Endocrine Abstracts

Introduction: Adrenocortical carcinoma is a rare type of cancer that usually has a dismal prognosis. The concurrent hormonal excess of some of these tumours can have an additional negative impact on patients´ morbidity and mortality.

Clinical Case: We present the case of a 57-year-old woman diagnosed with stage IV adrenocortical carcinoma, with liver and bone metastasis, and associated ACTH-independent Cushing syndrome and hyperandrogenism. The patient was started on cytotoxic chemotherapy (etoposide, doxorubicin and platinium), mitotane and metyrapone to control both tumour burden and hormonal secretion. Due to hypercortisolism persistence (salivary midnight cortisol 3.01 ug/dl; morning cortisol 50.8 mg/dl; ACTH<10 pg/ml), mitotane was uptitrated to 6 g/day, metyrapone to 750 mg 3id and ketoconazole was initiated. Uncontrolled Cushing’s led to recurrent infections with the need for hospital admission including to the intensive care unit. Recurrent severe hypokalaemia (K+ 2.7 mEq/l) episodes also prompted prolonged hospital stays with the need for both oral intravenous potassium chloride (100 mEq/l) and spironolactone addition. Medical therapy was further uptitrated exploring their maximum dosages (mitotane 8 gr/day; metyrapone 2.250 mg/day; ketoconazole 1.600 mg/day; spironolactone 400 mg/day). Despite all these efforts, neither mitotane levels reached therapeutic levels nor did Cushing tests attain normal values. Serial imaging studies revealed structural neoplastic progression. The patient’s persistent nausea and vomiting limited her compliance with the therapeutic plan. To reduce the daily pill intake and improve medication tolerability, osilodrostat was requested and approved but the patient died due to disease progression and uncontrolled Cushing before starting this new adrenolytic agent.

Discussion: Pharmacologic management of these patients is challenging considering that metyrapone is useful for Cushing’s control but promotes hypokalaemia. Low potassium levels can be mitigated by adding spironolactone, but this agent can cause a decrease in the adrenolytic effects of mitotane. In these cases, uncontrolled hypercortisolism may have a higher impact on patients’ prognosis than the tumour burden itself.